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有机氯农药暴露于人卵巢表面上皮细胞后诱导上皮细胞及炎症介质产生:一项体外研究。

Organochlorine pesticides induce epithelial as well as inflammatory mediators following exposure to human ovarian surface epithelial cells: An in vitro study.

机构信息

Department of Biochemistry, Environmental Biochemistry and Molecular Biology Laboratory, University College of Medical Sciences and G.T.B. Hospital (University of Delhi), Delhi, India.

Department of Obstetrics and Gynecology, University College of Medical Sciences and G.T.B. Hospital (University of Delhi), Delhi, India.

出版信息

J Biochem Mol Toxicol. 2022 Nov;36(11):e23191. doi: 10.1002/jbt.23191. Epub 2022 Aug 10.

Abstract

Although studies have suggested organochlorine pesticides (OCPs) exposure increased the risk of epithelial ovarian cancer, the mechanisms underlying its potential tumorigenic effects in the human ovary are not well understood. In this study, we investigated the impact of dichlorodiphenyldichloroethylene (DDE), endosulfan, and heptachlor exposure on epithelial cadherin (E-cadherin) and proinflammatory mediators in human ovary surface epithelial (HOSE) cells. We found that DDE, endosulfan, and heptachlor exposure resulted in epithelial differentiation accompanied by upregulation of E-cadherin expression and overexpression of proinflammatory cytokines (TNFα, IL-1β, and IL-6) in HOSE cells. The epithelial differentiation may accelerate HOSE cells to inclusion body formation, a common site for ovarian cancer initiation and persistent exposure to OCPs creates a chronic inflammatory microenvironment that may promote the neoplastic transformation of HOSE cells within the inclusion cyst.

摘要

尽管研究表明有机氯农药(OCPs)暴露会增加患上皮性卵巢癌的风险,但 OCPs 在上皮性卵巢中的潜在致癌作用的机制尚不清楚。在这项研究中,我们研究了二氯二苯二氯乙烯(DDE)、硫丹和七氯暴露对人卵巢表面上皮(HOSE)细胞上皮钙黏蛋白(E-cadherin)和促炎介质的影响。我们发现,DDE、硫丹和七氯暴露导致上皮分化,同时伴有 E-cadherin 表达上调和促炎细胞因子(TNFα、IL-1β 和 IL-6)过度表达。上皮分化可能加速 HOSE 细胞形成包涵体,这是卵巢癌起始的常见部位,而持续暴露于 OCPs 会产生慢性炎症微环境,可能促进包涵囊肿内 HOSE 细胞的肿瘤转化。

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